: This is a proposal for a competing renewal of a postdoctoral training grant located in a multidisciplinary setting at the University of Michigan. The 13 faculty are all NIDA grantees (or Co-Pls) and have expertise in the neurobiology of substance abuse, with particular emphasis on the area of opioid and psychostimulant drugs. The focus of the proposal is the training of Ph.D. and M.D. postdoctoral fellows in state-of-the-art approaches for studying mechanisms underlying abuse of psychoactive drugs. This includes studying the genetic, developmental and environmental factors that lead to vulnerability to substance abuse: the mode of action of drugs of abuse at the molecular, cellular, anatomical and behavioral levels; and the long-term consequences of pschoactive drugs on the brain, as mediated through mechanisms of neural plasticity. The working assumption is that the functional and structural brain remodeling associated with chronic drug use lies at the basis of tolerance, sensitization, physical dependence, and psychological addiction to these drugs. The drug abuse research community at the University of Michigan is of high quality and has a long history in the field. Beyond their individual strengths, the training faculty members have long-term scientific and training relationships with each other. These historical strengths have recently been significantly enhanced with a number of new initiatives' at the University of Michigan, designed to facilitate life sciences research in general, and neuroscience research in particular. They include state-of-the-art tools for mouse and rat genetics, genomics, proteomics, and informatics. Thus, our trainees will profit from a highly sophisticated, yet extremely supportive, research and training environment.